After treatment with SIRT1 shRNA, the protective effects of roflumilast on ISO-induced cardiac hypertrophy, oxidative stress, and mitochondrial damage were abolished (Fig. 4J through 4M, Figure S10C through S10E), and roflumilast-induced colocalization of PINK1, Parkin and LC3B with MitoTracker was also attenuated (Figure S11A through S11C). Here, PRKN is linked to cardiac hypertrophy.